Hanna Jason A, Bordeaux Jennifer, Rimm David L, Agarwal Seema
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Adv Cancer Res. 2009;103:1-23. doi: 10.1016/S0065-230X(09)03001-2.
The hepatocyte growth factor (HGF) and its receptor, the Met receptor tyrosine kinase, form a signaling network promoting cell proliferation, invasion, and survival in normal and cancer cells. Improper regulation of this pathway is attributed to many cancer types through overexpression, activating mutations, or autocrine loop formation. Many studies describe the localization of Met as membranous/cytoplasmic, but some studies using antibodies targeted to the C-terminal domain of Met report nuclear localization. This chapter seeks to highlight the histopathology and expression of Met in cancer and its association with clinicopathological characteristics. We also discuss recent studies of the proteolytic processing of Met and effects of the processing on the subcellular localization of Met. Finally, we comment on Met as a therapeutic target for cancer treatment.
肝细胞生长因子（HGF）及其受体——Met受体酪氨酸激酶，形成了一个信号网络，在正常细胞和癌细胞中促进细胞增殖、侵袭和存活。该信号通路的调控异常通过过表达、激活突变或自分泌环形成等方式，与多种癌症类型相关。许多研究将Met的定位描述为膜性/胞浆性，但一些使用靶向Met C末端结构域抗体的研究报告称Met存在核定位。本章旨在强调Met在癌症中的组织病理学和表达情况及其与临床病理特征的关联。我们还将讨论Met蛋白水解加工的最新研究以及该加工对Met亚细胞定位的影响。最后，我们对Met作为癌症治疗的治疗靶点进行评论。
